Alendronate sodium, the sodium salt of alendronic acid, also known as 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid monosodium, has the formula I: It is an agent for combating bone resorption in bone diseases including osteoporosis and Paget's disease.
Various methods for preparing alendronic acid are known in the art and have been disclosed in M. I. Kabachnik et al., Synthesis and Acid-Base and Complexing Properties of Amino-Substituted α-Hydroxyalkylidene-diphosphonic Acids, Izv. Akad. Nauk USSR, Ser. Khim, 2,433 (1978) and in U.S. Pat. Nos. 4,407,761, 4,621,077, 4,705,651, 5,039,819 and 5,159,108.
U.S. Pat. No. 4,922,007 describes the preparation of a trihydrate of alendronate sodium by reaction of 4-aminobutyric acid with phosphorous acid and phosphorous trichloride in the presence of methanesulfonic acid followed by the addition of sodium hydroxide.
The present invention prov:des new hydrate forms of alendronate sodium, having water content of 1.3 to 11.7 percent, and processes for their manufacture. Moreover, the present invention provides new crystalline forms of alendronate sodium, designated forms B, D, E, F, G and H, and processes for the manufacture thereof.